10-99955492-T-C
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_015221.4(DNMBP):āc.1982A>Gā(p.Lys661Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00875 in 1,600,692 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: š 0.0060 ( 7 hom., cov: 32)
Exomes š: 0.0090 ( 84 hom. )
Consequence
DNMBP
NM_015221.4 missense
NM_015221.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.366
Genes affected
DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0036566257).
BP6
Variant 10-99955492-T-C is Benign according to our data. Variant chr10-99955492-T-C is described in ClinVar as [Benign]. Clinvar id is 3034405.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMBP | NM_015221.4 | c.1982A>G | p.Lys661Arg | missense_variant | 4/17 | ENST00000324109.9 | NP_056036.1 | |
DNMBP-AS1 | NR_024130.3 | n.177-182T>C | intron_variant, non_coding_transcript_variant | |||||
DNMBP | XM_011539559.3 | c.1982A>G | p.Lys661Arg | missense_variant | 5/18 | XP_011537861.1 | ||
DNMBP | XM_047424910.1 | c.1982A>G | p.Lys661Arg | missense_variant | 5/18 | XP_047280866.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMBP | ENST00000324109.9 | c.1982A>G | p.Lys661Arg | missense_variant | 4/17 | 1 | NM_015221.4 | ENSP00000315659 | P1 | |
DNMBP-AS1 | ENST00000661385.1 | n.223-990T>C | intron_variant, non_coding_transcript_variant | |||||||
DNMBP-AS1 | ENST00000434409.2 | n.173-182T>C | intron_variant, non_coding_transcript_variant | 2 | ||||||
DNMBP-AS1 | ENST00000661150.1 | n.177-1297T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00598 AC: 910AN: 152120Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00523 AC: 1263AN: 241364Hom.: 10 AF XY: 0.00553 AC XY: 721AN XY: 130334
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GnomAD4 exome AF: 0.00904 AC: 13093AN: 1448454Hom.: 84 Cov.: 31 AF XY: 0.00875 AC XY: 6290AN XY: 719104
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GnomAD4 genome AF: 0.00598 AC: 910AN: 152238Hom.: 7 Cov.: 32 AF XY: 0.00521 AC XY: 388AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DNMBP-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at